The theme of the Imaging Core is molecular imaging of mouse models of human breast cancer. The Core provides individual projects with non-invasive, quantitative imaging-based capabilities for metabolic and genetic characterization of tumors and their microenvironment, including in vivo trafficking of tumor cells. This will be accomplished by monitoring of directly-targeting probes and of the expression of single and multi-modality reporter genes using optical (bioluminescence and fluorescence), radionuclide (PET, SPECT, and autoradiography), MRI/MRS, CT, and US) imaging. These quantitative, non-invasive imaging techniques are well-established at MSKCC for both smallanimal and patient imaging studies. They are quantitative and non-invasive and thus readily adaptable to longitudinal studies. The Imaging Core can readily provide [18F]-FDG, [18F]-FLT, [18F]-ACBC , and [I8F]-FMISO or [124I]-IAZG microPET to all RPs for non-invasive assessment of tumor glycolysis, cell proliferation, amino transport, and hypoxia, respectively, in mouse models of breast cancer. Further, a number of inducible reporter systems for non-invasive in vivo imaging in small animals have been developed. These reporter systems are all multi-modality reporters and include the capability for fluorescence, bioluminescence and radionuclide imaging. In addition to p53 and DFHR, the list of inducible reporters includes NFAT, FIRE (hypoxia response element - hypoxia inducible factor), E2F, Forkhead factor (FOXO), heat shock protein 70 (HSP70) and TGFp. A general two-step strategy is generally pursued in probe development: first, to establish and validate imaging and non-invasive assay techniques in experimental animals, and second, to translate where appropriate selected aspects of our imaging technology to patient studies within the context of the Research Projects (RPs) proposed in this Application. The Imaging Core will actively and directly support all five RPs, led by Harold Varmus, Joan Massague, Neil Rosen, Maria Jasin, and Robert Benezra, respectively.